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阿伐考潘,一种新型的 C5a 受体拮抗剂,用于治疗严重的抗中性粒细胞胞质抗体相关性血管炎。

Avacopan, a Novel Competitive C5a Receptor Antagonist, for Severe Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

机构信息

School of Medicine, LSU Health Sciences Center New Orleans, 1901 Gravier Street, New Orleans, LA, 70112, USA.

School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103, USA.

出版信息

Clin Drug Investig. 2023 Aug;43(8):595-603. doi: 10.1007/s40261-023-01298-z. Epub 2023 Aug 18.

Abstract

Avacopan is a relatively novel drug with complement antagonizing properties, and it has demonstrated promising outcomes in treating antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. This review article seeks to investigate the current standard of care for ANCA vasculitis with the combination of avacopan. The current standard therapy involves the usage of daily corticosteroids in addition to either cyclophosphamide or rituximab; however, prolonged use of corticosteroids is known to be associated with various adverse effects. Avacopan was introduced as a possible substitution to alleviate high-corticosteroid dosages. It functions through competitive inhibition of the C5a receptor in the complement system and results in the reduction of neutrophil activation and migration to sites of inflammation. Clinical trials have observed the efficacy of avacopan both in conjunction with standard therapy with corticosteroids and without corticosteroids. The use of avacopan was able to achieve disease remission and improve renal function in patients with ANCA-associated vasculitis. Additionally, the novel treatment did not increase the risk of adverse events during treatment, while also lowering the toxic effects associated with corticosteroid usage. In summary, current evidence supports the success and safety of administering avacopan to treat patients with ANCA-associated vasculitis. Additional clinical trials are warranted to identify optimal dosage and method in using avacopan in the clinical setting.

摘要

阿伐考帕是一种具有补体拮抗作用的新型药物,在治疗抗中性粒细胞胞质抗体(ANCA)相关性血管炎方面显示出良好的疗效。本文旨在探讨阿伐考帕联合治疗 ANCA 血管炎的现有标准治疗方案。目前的标准治疗方案包括每日使用皮质类固醇,同时使用环磷酰胺或利妥昔单抗;然而,长期使用皮质类固醇已知会引起各种不良反应。阿伐考帕作为一种可能的替代药物被引入,以减轻高剂量皮质类固醇的使用。它通过竞争性抑制补体系统中的 C5a 受体起作用,从而减少中性粒细胞的激活和向炎症部位的迁移。临床试验观察到阿伐考帕联合或不联合皮质类固醇标准治疗方案在治疗 ANCA 相关性血管炎方面的疗效。阿伐考帕的使用能够使患者达到疾病缓解并改善肾功能。此外,这种新的治疗方法并没有增加治疗期间不良事件的风险,同时降低了与皮质类固醇使用相关的毒性作用。总之,现有证据支持使用阿伐考帕治疗 ANCA 相关性血管炎的疗效和安全性。需要进一步的临床试验来确定在临床实践中使用阿伐考帕的最佳剂量和方法。

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